effect and safety mabs administration m.3243a>g mutation carriers

Conditions: Mitochondrial Myopathies

Summary: the first primary objective is to assess the effect of three intra-arterial administrations of autologous mesoangioblasts (mabs) with respect to improving muscle strength and reduce fatigue of the treated biceps brachii (bb) compared to the untreated bb. the second primary objective is safety of three intra-arterial administrations of autologous mabs, which the investigators will assess by monitoring (serious) adverse events ((s)aes), blood flow in left arm pre- and post-intervention, and neurological vital signs during 8h post-intervention observation in the hospital. secondary objectives are to assess changes in muscle mass of the treated and untreated bb muscle, and microscopic changes and m.3243a\>g mutation load at tissue level in treated biceps brachii (bb) muscle at baseline and after treatment. up to 20 adult m.3243a\>g patients will undergo a \~30mg m. biceps brachii muscle biopsy at visit 1. the first six eligible patients will enroll the clinical study based on their m.3243a\>g mutation load in skeletal muscle (50-90%) and mesoangioblasts (\<10%), and on a decreased bb muscle strength and increased fatigue. these 6 selected patients will visit the maastricht university medical center for 8 additional times. from each patient, during visit 2 till 9: * bb muscle biopsies of the left arm will be collected (1x \~130 mg at visit 2 and 1x \~30mg at visit 9) * mri of the bb muscles in both arms will be performed (visit 2 and 9). * autologous mabs will be injected into the left arm via axillary artery delivery. angiography will be performed before and after infusion to assess vascular obstructions, and the participant will be monitored in the hospital for 8 hours (visit 4,6,8). * tc99m macroaggregated albumin (maa) is infused to quantify blood flow to the bb muscle (visit 4). * a bout of maximal eccentric exercise of bb muscles on both sides will be executed at visit 3, 5 and 7. * bb muscle strength will be assessed using a biodex dynamometer (visit 3-9) * venous blood samples will be taken for assessing muscle damage and inflammation markers (visit 3-9), kidney functioning, coagulation and viral screening (visit 1 and 2).


Eligibility criteria:
inclusion criteria: * written informed consent * age: 18-64 * sex: male/female * patients with the m.3243a\>g mutation load of 50%-90% determined in skeletal muscle or derived from age-corrected calculation of blood m.3243a\>g mutation load exclusion criteria: a potential subject who meets any of the following criteria will be excluded from participation in this study: * use of dabigatran, apixaban, edoxaban or rivaroxaban (doacs) as anti-coagulants * have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women) * current history of drug abuse * deficient immune system or autoimmune disease * significant concurrent illness * ongoing participation in other clinical trials with intervention * pregnant or lactating women * psychiatric or other disorders likely to impact on informed consent * patients unable and/or unwilling to comply with treatment and study instructions * a history of strokes with signs of extra-pyramidal or pyramidal syndrome * allergy for contrast fluid * peripheral signs of ischemia or vasculopathy * claustrophobia * metal implants * any other factor that in the opinion of the investigator excludes the patient from the study

Keywords: m.3243a>g mesoangioblasts